Adaptation, the ability of the eye to adjust its sensitivity to match the available light, is a very important aspect of normal healthy vision. When the eye does not adapt properly it becomes impossible to see in both dim and bright light. One of the difficulties of dealing with visual problems of this sort is the fact that the whole process of adaptation is rather poorly understood. From studies of cellular responses in cold-blooded vertebrates we know that exposure to light modifies the responses properties of both photoreceptors and second order cells. Studies on turtles and fish show that rod and cone photoreceptors are strongly adapted by background light. However, an increasing body of evidence indicates that in the eyes of mammals receptor adaptation is limited importance in controlling the sensitivity of rod and possibly also cone driven responses. One of the objectives of this proposal is understanding how these latter network mechanisms cause thresholds to elevate, responses to speed-up, and dynamic range to be modified. Work on the turtle has revealed that adaptation in cones involves the cooperation of groups of photoreceptors. These interactions in turtle may be a model for the adaptational changes that occur downstream from receptors in mammals. How these cells communicate with one another is an unsolved mystery we intend to investigate. One of our main goals is to understand the electrical, diffusional, and synaptic processes that underlie the neural interactions by which adaptation spreads between cones. Electrical influences can be examined by passing current through a microelectrode inserted into one cone and recording the effect this has on the responses recorded with a second electrode inserted into a neighboring cone. If the interaction is electrical it is important to know whether the effect is on the plasma membrane of the cell or on the transduction mechanism. Diffusible extracellular desensitizing agents can take considerable time to get from their site of generation to their site of action. Thus examining the time course of light adaptation can provide evidence for or against this hypothesis. A crisp answer to this question requires one to unravel the physiological components of adaptational smear from those due to scattered light. We also hope to be able to measure the light spread and to quantify its effects on sensitivity by using a computer model as a tool. If a diffusible transmitter is implicated then the effluent from a perfusion system containing a light adapted retina would be collected and analyzed, and its activity assessed by determining its ability to desensitize a dark adapted retina. To test is synaptic processes are involved we will treat the retina with agents that block chemical synaptic transmission and see whether lateral adaptation is also blocked.